PPARgamma is an orphan nuclear receptor implicated in diabetes, hypercholesterolemia, colon cancer, and breast cancer that has no known antagonist. We are designing, synthesizing, and testing candidate antagonists for PPARgamma. Our designs focus on the relationship between chemical structures of known agonists and antagonists for other nuclear receptors to modify known thiazolidinedione compounds to become PPARgamma antagonists. SAR data on these molecules along with sequence alignments and homology models evaluated using Computer Graphics Laboratory resources help us choose promising directions to follow in the design of new candidate molecules.